Myocardial ischemia‐reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease (CHD). Mitochondrial dysfunction is the crucial factor of MIRI; oxidative stress caused by mitochondrial reactive oxygen species (ROS) aggravates myocardial cell damage through the mitochondria‐dependent apoptosis pathway. Asiatic acid (AA) is a type of pentacyclic triterpene compound purified from the traditional Chinese medicine Centella asiatica, and its protective pharmacological activities have been reported in various disease models. This study is aimed at investigating the protective effects of AA and the underlying mechanisms in MIRI. To achieve this goal, an animal model of MIRI in vivo and a cell model of oxygen‐glucose deprivation/reperfusion (OGD/R) in vitro were established. The results show that AA exerts a protective effect on MIRI by improving cardiac function and reducing cardiomyocyte damage. Due to its antioxidant properties, AA alleviates mitochondrial oxidative stress, as evidenced by the stable mitochondrial structure, maintained mitochondrial membrane potential (MMP), and reduced ROS generation, otherwise due to its antiapoptotic properties. AA inhibits the mitogen‐activated protein kinase (MAPK)/mitochondria‐dependent apoptosis pathway, as evidenced by the limited phosphorylation of p38‐MAPK and JNK‐MAPK, balanced proportion of Bcl‐2/Bax, reduced cytochrome c release, inhibition of caspase cascade, and reduced apoptosis. In conclusion, our study confirms that AA exerts cardiac‐protective effects by regulating ROS‐induced oxidative stress via the MAPK/mitochondria‐dependent apoptosis pathway; the results provide new evidence that AA may represent a potential treatment for CHD patients.

Resveratrol is a kind of iPolyphenols widely existing in herbal medicine. Here we aim to investigate whether resveratrol can reduce the degree of myocardial ischemia/reperfusion (IR) injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of resveratrol in protecting myocardial cells. The primary rat cardiomyocytes were used to establish an ischemia/reperfusion model in vitro, and a series of routine biochemical experiments were conducted to explore the antioxidant and anti-apoptotic effects of resveratrol in myocardial ischemia-reperfusion injury. Compared with that of the simulated ischemia-refusion (SIR) group, cell viability in the SIR and resveratrol co-treatment groups increased significantly (P < 0.001), the release of lactate dehydrogenase (LDH) and creatine kinase MB (CKMB) decreased, the positive rate of reactive oxygen species (ROS) in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, resveratrol can activate PI3K/AKT signaling pathway. PI3K siRNA can inhibit the PI3K/AKT signaling mediated by resveratrol. The addition of resveratrol can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the malondialdehyde (MDA), which indicates that the oxidative damage of mitochondria induced by resveratrol was significantly weakened. The mitochondrial functional changes induced by resveratrol can be reversed by PI3K siRNA. In conclusion, our study shows that resveratrol can reduce ROS in cardiomyocytes by PI3K/AKT signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SR.

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.

A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe²⁺ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe²⁺ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis.

Background: The neutrophil-lymphocyte ratio (NLR) has been recognized as a useful marker of poor prognosis in non-cardiac surgery patients. But, the prognostic function of NLR in cardiovascular surgery patients still largely unknown. The aim of this study was to explore the relationship between postoperative NLR and mortality in cardiac surgery patients. Methods: Clinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Postoperative day 1 (POD-1) NLR of the patients was calculated. All patients were divided into two groups according to the cut-off value of NLR, which was determined using the receiver operating characteristic (ROC) curve and Youden Index. The primary death outcomes were 30-day, 90-day and 1-year mortality. Cox proportional hazard analysis was performed to assess the associations between NLR and 1-year mortality. Logistic analysis was performed to assess the associations between NLR and other outcomes. Multivariate analyses were used to control for confounders. Results: A total of 2,707 cardiac surgery patients were included in this study. The cut-off value of postoperative NLR was 7.28. Elevated postoperative NLR was associated with increased death outcomes including 30-day mortality [adjusted odds ratio (OR) 2.25, P=0.019], 90-day mortality (adjusted OR 2.49, P=0.001) and 1-year mortality [adjusted hazard ratio (HR) 1.58, P=0.03] of cardiac surgery in cox proportional hazard model. Elevated NLR was also associated with increased risk of continuous renal replacement therapy (CRRT) rate (adjusted OR 3.01, P=0.004), prolonged ICU stays (adjusted OR 2.55, P<0.001), prolonged hospital stays (adjusted OR 3.32, P<0.001) and duration of ventilatory support (adjusted OR 4.16, P<0.001) after adjusting confounders. Conclusions: Elevated postoperative NLR was significantly associated with increased short-term and long-term mortality, CRRT rate, longer ICU and hospital stay, prolonged ventilation in patients undergoing cardiac surgery. NLR is promising to be a readily available and independent prognostic biomarker for patients with cardiac surgery.

Myocardial ischemia‑reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease. The excessive accumulation of reactive oxygen species (ROS) during MIRI induces the overactivation of an autophagic response, which aggravates myocardial cell damage. Asiatic acid (AA) is a triterpenoid compound, which is extracted from Centella asiatica and exhibits a variety of pharmacological effects such as hepatoprotective, neuroprotective and antioxidant. However, the association of AA with autophagy in MIRI is not fully understood. In the present study, the positive effects of AA in MIRI injury were determined via establishing a MIRI mouse model. Pre‑treatment with AA was indicated to improve cardiac function and decrease cardiomyocyte autophagy in mice subjected to MIRI. To examine the protective effects of AA and the underlying mechanisms in MIRI, a cardiomyocyte glucose deprivation/reperfusion (OGD) model was established. The administration of AA decreased the levels of ROS and malondialdehyde and increased the levels of superoxide dismutase activity in OGD‑treated cells. Using western blotting, it was demonstrated that treatment with AA decreased the phosphorylation of p38 and increased the expression of Bcl‑2 in OGD‑treated cells. Additionally, the expression of autophagy markers, including beclin‑1 and the microtubule‑associated proteins 1A/1B light chain 3B II/I ratio, were also decreased in AA treated cells compared with OGD‑treated cells. These results demonstrated that AA pretreatment protected cardiomyocytes from ROS‑mediated autophagy via a p38 mitogen‑activated protein kinase/Bcl‑2/beclin‑1 signaling pathway in MIRI.